The requirement for continued gonadotropin support to maintain primate luteal function is well established. These studies were designed to determine (a) the optimal regimen of third generation GnRH antagonist to abolish luteal function, and (b) the amount and frequency of LH replacement required to maintain luteal progesterone production following GnRH antagonist titration. Beginning on day 6 of the luteal phase, monkeys received the GnRH antagonist Antide in either a single dose of 3 (n=1) or 5 (n=4) mg/kg body weight or 3 mg/kg for 3 consecutive days (n=3); daily serum progesterone was determined by RIA for 4 days following initation of treatment. A single injection of Antide at either dose suppressed progesterone production within 1 day of treatment (p<0.05, 5 mg/kg group). In both groups, serum progesterone was not different from pretreatment levels by day 4. Administration of Antide (3 mg/kg) on day 6-8 reduced serum progesterone below 1 ng/ml within 1 day (p<0.05) and maintained these low levels for the entire sampling period (p<0.05). To determine the amount of LH required to sustain normal luteal progesterone production in GnRH antagonist treated monkeys, Antide (3 mg/kg for 3 days) was administered concomitant with recombinant human LH at 5 or 10 IU/injection 3 times daily (n=3/group) throughout the test interval. In animals treated with Antide + 10 IU LH, serum progesterone was elevated above pretreatment levels within 1 day of initiation of treatment (3.4 q 0.7 vs. 7.1 q 0.8 ng/ml, p=0.05). Treatment with Antide + 5 IU LH resulted in similar progesterone concentrations before (4.7 q 1.3 ng/ml) and after (5.4 q 1.3 ng/ml) initiation of treatment, and progesterone levels typical of the luteal phase were measured throughout the test interval. The use of GnRH antagonist alone and with LH replacement provides a valuable model to study the role of gonadotropin in the maintenance of the primate corpus luteum during the luteal phase, as well as allow the use of specific inhibitors of steroidogenesis to examine the effects on luteal structure and function during continued exogenous gonadotropin support.